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A mechanistic model for naive CD4 T cell homeostasis in healthy adults and children.

Hapuarachchi T, Lewis J, Callard RE - Front Immunol (2013)

Bottom Line: Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity.The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells.It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

View Article: PubMed Central - PubMed

Affiliation: Institute of Child Health and CoMPLEX, University College London , London , UK.

ABSTRACT
The size and composition of the T lymphocyte compartment is subject to strict homeostatic regulation and is remarkably stable throughout life in spite of variable dynamics in cell production and death during T cell development and immune responses. Homeostasis is achieved by careful orchestration of lymphocyte survival and cell division. New T cells are generated from the thymus and the number of peripheral T cells is regulated by controlling survival and proliferation. How these processes combine is however very complex. Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity. Proliferation of new naive T cells plays a crucial role for maintaining numbers but at a potential cost to TCR repertoire diversity. A mechanistic two-compartment model of T cell homeostasis is described here that includes specific terms for thymic output, cell proliferation, and cell death of both resting and dividing cells. The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells. It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

No MeSH data available.


Effect on T cell dynamics of changes in resource concentration for entry into cell division (ε) and survival (ρ). Other parameters are as in Table 1. It is noteworthy that the homeostatic equilibrium is more sensitive to changes in the resource parameter (ε) for entry into cell division than the parameter (ρ) for survival.
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Figure 5: Effect on T cell dynamics of changes in resource concentration for entry into cell division (ε) and survival (ρ). Other parameters are as in Table 1. It is noteworthy that the homeostatic equilibrium is more sensitive to changes in the resource parameter (ε) for entry into cell division than the parameter (ρ) for survival.

Mentions: Next, we investigated the effect of the amount of resource available for cell division (ε) and cell survival (ρ) (Figure 5). Consistent with competition between naive CD4 T cells for a resource such as spMHC and/or IL7 in order to survive and undergo cell division, the number of cells at homeostatic equilibrium decreased as the resource terms ε for proliferation and ρ for survival decreased. Interestingly, the rate of entry into cell cycle was significantly more sensitive than survival to changes in resource concentration, consistent with different thresholds for proliferation and survival as previously described (27).


A mechanistic model for naive CD4 T cell homeostasis in healthy adults and children.

Hapuarachchi T, Lewis J, Callard RE - Front Immunol (2013)

Effect on T cell dynamics of changes in resource concentration for entry into cell division (ε) and survival (ρ). Other parameters are as in Table 1. It is noteworthy that the homeostatic equilibrium is more sensitive to changes in the resource parameter (ε) for entry into cell division than the parameter (ρ) for survival.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3822783&req=5

Figure 5: Effect on T cell dynamics of changes in resource concentration for entry into cell division (ε) and survival (ρ). Other parameters are as in Table 1. It is noteworthy that the homeostatic equilibrium is more sensitive to changes in the resource parameter (ε) for entry into cell division than the parameter (ρ) for survival.
Mentions: Next, we investigated the effect of the amount of resource available for cell division (ε) and cell survival (ρ) (Figure 5). Consistent with competition between naive CD4 T cells for a resource such as spMHC and/or IL7 in order to survive and undergo cell division, the number of cells at homeostatic equilibrium decreased as the resource terms ε for proliferation and ρ for survival decreased. Interestingly, the rate of entry into cell cycle was significantly more sensitive than survival to changes in resource concentration, consistent with different thresholds for proliferation and survival as previously described (27).

Bottom Line: Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity.The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells.It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

View Article: PubMed Central - PubMed

Affiliation: Institute of Child Health and CoMPLEX, University College London , London , UK.

ABSTRACT
The size and composition of the T lymphocyte compartment is subject to strict homeostatic regulation and is remarkably stable throughout life in spite of variable dynamics in cell production and death during T cell development and immune responses. Homeostasis is achieved by careful orchestration of lymphocyte survival and cell division. New T cells are generated from the thymus and the number of peripheral T cells is regulated by controlling survival and proliferation. How these processes combine is however very complex. Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity. Proliferation of new naive T cells plays a crucial role for maintaining numbers but at a potential cost to TCR repertoire diversity. A mechanistic two-compartment model of T cell homeostasis is described here that includes specific terms for thymic output, cell proliferation, and cell death of both resting and dividing cells. The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells. It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

No MeSH data available.